title: VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses.
abstract: The immunoglobulin (Ig) superfamily consists of many critical immune regulators, including the B7 family ligands and receptors. In this study, we identify a novel and structurally distinct Ig superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family ligand PD-L1. This molecule is designated V-domain Ig suppressor of T cell activation (VISTA). VISTA is primarily expressed on hematopoietic cells, and VISTA expression is highly regulated on myeloid antigen-presenting cells (APCs) and T cells. A soluble VISTA-Ig fusion protein or VISTA expression on APCs inhibits T cell proliferation and cytokine production in vitro. A VISTA-specific monoclonal antibody interferes with VISTA-induced suppression of T cell responses by VISTA-expressing APCs in vitro. Furthermore, anti-VISTA treatment exacerbates the development of the T cell-mediated autoimmune disease experimental autoimmune encephalomyelitis in mice. Finally, VISTA overexpression on tumor cells interferes with protective antitumor immunity in vivo in mice. These findings show that VISTA, a novel immunoregulatory molecule, has functional activities that are nonredundant with other Ig superfamily members and may play a role in the development of autoimmunity and immune surveillance in cancer.
authors.affiliation: Department of Microbiology and Immunology, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03766, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Rotem
authors.initials: R
authors.lastname: Rubinstein
authors.forename: Janet L
authors.initials: JL
authors.lastname: Lines
authors.forename: Anna
authors.initials: A
authors.lastname: Wasiuk
authors.forename: Cory
authors.initials: C
authors.lastname: Ahonen
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Guo
authors.forename: Li-Fan
authors.initials: LF
authors.lastname: Lu
authors.forename: David
authors.initials: D
authors.lastname: Gondek
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Roy A
authors.initials: RA
authors.lastname: Fava
authors.forename: Andras
authors.initials: A
authors.lastname: Fiser
authors.forename: Steve
authors.initials: S
authors.lastname: Almo
authors.forename: Randolph J
authors.initials: RJ
authors.lastname: Noelle
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology; D060887:B7 Antigens / Q000276:immunology* / Q000502:physiology*; D018122:B7-1 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007136:Immunoglobulins / Q000276:immunology* / Q000502:physiology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D060887:B7 Antigens; D018122:B7-1 Antigen; D007136:Immunoglobulins; D008024:Ligands; C000588758:VSIR protein, human